Time to Act is Now: Paediatrics Medicines Development in the UK

In this post, Annabel Bonsu, senior manager of PPD regulatory affairs of our Cambridge, U.K., office and member of PPD’s Regulatory Affairs Pediatric Forum, discusses obligations sponsors will face as new application procedures are about to take effect with the conclusion of the BREXIT transition period on 31 December 2020. Paediatric applications will be regulated in the U.K. by the Medicines Healthcare and Regulatory Agency (MHRA) beginning 1 January 2021. If you have not acted yet, the time is now.

Understanding the key changes

In making these changes, the MHRA aims to simplify the process for paediatric investigator plans (PIPs) by offering sponsors a paediatric assessment on a case-by-case basis where feasible. While the scientific content of a U.K. PIP will be aligned with EMA guidance documents, the scientific argument and its relevance to the U.K. population will play a key role in the MHRA decision-making process.

The good news for sponsors is European Union (EU) PIPs, modifications and waivers previously agreed to prior to the first of the new year will generally be adopted as U.K. PIPs without reassessment by the MHRA as a transitional provision. This assumes there have been no subsequent modifications by the sponsor leading to divergence between the EU and U.K. MHRA decision and taking into consideration parameters such as unmet U.K. paediatric needs. However, in cases where a final opinion has not been issued by the EU Paediatric Committee (PDCO) or an initial U.K. paediatric application is yet to be made, submissions will need to be completed via the MHRA PIPs section of the submissions home page for full MHRA assessment. Detailed guidance documents^{1, 2} issued by the MHRA cover the new framework and include these key areas:

• U.K. PIPs procedures
• Submission, processing and assessment for completed paediatric studies
• Applications for modification and requests for class waivers or deferrals of agreed PIPs
  • Class waivers will in principle be adopted by the MHRA from the current European Medicines Agency (EMA) list,³ which may potentially be subject to future MHRA changes
• Operation of PIPs compliance check in accordance with Human Medicines Regulations (HMR) 2012 as amended by the Human Medicines (Amendment, etc.) (EU Exit) Regulations 2019
  • A clinical study report must be provided by the sponsor in support of a compliance check
  • The MHRA recommendation is that sponsors request a compliance check by MHRA at least one month prior to the planned submission of a regulatory application when possible to minimize delays
• Annual reporting requirements for each agreed U.K. PIPs
• Paediatric requirements for Marketing Authorisation Holders (MAHs).
• Results of paediatric studies will need to be submitted to the MHRA within six months of trial end per HMR 78A (13) and (14) (as amended)

Next steps

We understand these changes can be confusing and time consuming for sponsors. This is a novel process and poses the challenge of aligning the U.K. PIPs with the sponsor’s global strategy. The process requires a supportive regulatory team experienced in preparation of justifications for waivers or deferrals.

While this is a unique situation, the time to act is now. Sponsors should complete registration within the MHRA portal to make submissions before 1 January 2021⁴ and ensure that stakeholders appointed to perform submissions on behalf of the sponsor are appropriately delegated with user administration rights to minimize delay to future U.K. paediatric submissions.